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Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1
Oncolytic viruses are potent anticancer agents that replicate within and kill cancer cells rather than normal cells, and their selectivity is largely determined by oncogenic mutations. M1, a novel oncolytic virus strain, has been shown to target cancer cells, but the relationship between its cancer...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718955/ https://www.ncbi.nlm.nih.gov/pubmed/33037696 http://dx.doi.org/10.1002/1878-0261.12820 |
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author | Cai, Jing Lin, Kaiying Cai, Wei Lin, Yuan Liu, Xincheng Guo, Li Zhang, Jifu Xu, Wencang Lin, Ziqing Wong, Chun Wa Sander, Max Hu, Jun Yan, Guangmei Zhu, Wenbo Liang, Jiankai |
author_facet | Cai, Jing Lin, Kaiying Cai, Wei Lin, Yuan Liu, Xincheng Guo, Li Zhang, Jifu Xu, Wencang Lin, Ziqing Wong, Chun Wa Sander, Max Hu, Jun Yan, Guangmei Zhu, Wenbo Liang, Jiankai |
author_sort | Cai, Jing |
collection | PubMed |
description | Oncolytic viruses are potent anticancer agents that replicate within and kill cancer cells rather than normal cells, and their selectivity is largely determined by oncogenic mutations. M1, a novel oncolytic virus strain, has been shown to target cancer cells, but the relationship between its cancer selectivity and oncogenic signaling pathways is poorly understood. Here, we report that RAS mutation promotes the replication and oncolytic effect of M1 in cancer, and we further provide evidence that the inhibition of the RAS/RAF/MEK signaling axis suppresses M1 infection and the subsequent cytopathic effects. Transcriptome analysis revealed that the inhibition of RAS signaling upregulates the type I interferon antiviral response, and further RNA interference screen identified CDKN1A as a key downstream factor that inhibits viral infection. Gain‐ and loss‐of‐function experiments confirmed that CDKN1A inhibited the replication and oncolytic effect of M1 virus. Subsequent TCGA data mining and tissue microarray (TMA) analysis revealed that CDKN1A is commonly deficient in human cancers, suggesting extensive clinical application prospects for M1. Our report indicates that virotherapy is feasible for treating undruggable RAS‐driven cancers and provides reliable biomarkers for personalized cancer therapy. |
format | Online Article Text |
id | pubmed-7718955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77189552020-12-11 Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 Cai, Jing Lin, Kaiying Cai, Wei Lin, Yuan Liu, Xincheng Guo, Li Zhang, Jifu Xu, Wencang Lin, Ziqing Wong, Chun Wa Sander, Max Hu, Jun Yan, Guangmei Zhu, Wenbo Liang, Jiankai Mol Oncol Research Articles Oncolytic viruses are potent anticancer agents that replicate within and kill cancer cells rather than normal cells, and their selectivity is largely determined by oncogenic mutations. M1, a novel oncolytic virus strain, has been shown to target cancer cells, but the relationship between its cancer selectivity and oncogenic signaling pathways is poorly understood. Here, we report that RAS mutation promotes the replication and oncolytic effect of M1 in cancer, and we further provide evidence that the inhibition of the RAS/RAF/MEK signaling axis suppresses M1 infection and the subsequent cytopathic effects. Transcriptome analysis revealed that the inhibition of RAS signaling upregulates the type I interferon antiviral response, and further RNA interference screen identified CDKN1A as a key downstream factor that inhibits viral infection. Gain‐ and loss‐of‐function experiments confirmed that CDKN1A inhibited the replication and oncolytic effect of M1 virus. Subsequent TCGA data mining and tissue microarray (TMA) analysis revealed that CDKN1A is commonly deficient in human cancers, suggesting extensive clinical application prospects for M1. Our report indicates that virotherapy is feasible for treating undruggable RAS‐driven cancers and provides reliable biomarkers for personalized cancer therapy. John Wiley and Sons Inc. 2020-10-25 2020-12 /pmc/articles/PMC7718955/ /pubmed/33037696 http://dx.doi.org/10.1002/1878-0261.12820 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Cai, Jing Lin, Kaiying Cai, Wei Lin, Yuan Liu, Xincheng Guo, Li Zhang, Jifu Xu, Wencang Lin, Ziqing Wong, Chun Wa Sander, Max Hu, Jun Yan, Guangmei Zhu, Wenbo Liang, Jiankai Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title | Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title_full | Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title_fullStr | Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title_full_unstemmed | Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title_short | Tumors driven by RAS signaling harbor a natural vulnerability to oncolytic virus M1 |
title_sort | tumors driven by ras signaling harbor a natural vulnerability to oncolytic virus m1 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718955/ https://www.ncbi.nlm.nih.gov/pubmed/33037696 http://dx.doi.org/10.1002/1878-0261.12820 |
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